NZ207840A - Diphenylazomethine derivatives and pharmaceutical compositions - Google Patents
Diphenylazomethine derivatives and pharmaceutical compositionsInfo
- Publication number
- NZ207840A NZ207840A NZ207840A NZ20784084A NZ207840A NZ 207840 A NZ207840 A NZ 207840A NZ 207840 A NZ207840 A NZ 207840A NZ 20784084 A NZ20784084 A NZ 20784084A NZ 207840 A NZ207840 A NZ 207840A
- Authority
- NZ
- New Zealand
- Prior art keywords
- formula
- diphenylazomethine
- hydroxylated
- alkyl
- compound
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/32—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups
- C07C65/40—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing keto groups containing singly bound oxygen-containing groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
- C07C49/83—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups polycyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
New Zealand Paient Spedficaiion for Paient Number £07840
2 078 40
Priority Date(s): 14.
Complete Specification Filed: 1 Class: CP.a 61 . .'£« ,) . Jfi'?. J .Q&J . . .
Publication Date: .2 I. £EB .19&6 • • •
P.O. Journal, No:
COMPLETE SPECIFICATION
"HYDRQXYLATED DIPHENYLAZOMETHINES, THEIR PREPARATION AND PHARMACEUTICAL
COMPOSITIONS CONTAINING THEM"
AI We, SYNTHELABO, a French Body Corporate of 58, rue de la. Glaciere, 75621 Paris, France,
hereby declare the invention for which X / we pray that a patent may be granted to XitK/us, and the method by which it is to be performed, to be particularly described in and by the following statement:-
(followed by page la)
207840
- la-
HYDROXYLATED DIPHENYLAZOMETHINES, THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM The present invention relates to hydroxylated diphenylazomethines, their preparation and their use in 5 therapy.
The hydroxylated diphenylazomethines according to the invention correspond to the formula (I):
in which n is an integer from 1 to 4, X^, and X^, which may be the same or different, each represent a hydrogen atom,
a halogen atom, -OCH^ or a straight-chain or branched
C^_4~alkyl group, R represents -NH2, -OH or -0_M
P
(wherein M represents an alkali metal or alkaline earth metal of valency p) and Z represents -COOH, -COOalkyl,
-CONH2' -CONHalkyl, -CON(alky1)2, -CH2OH, -CH2Oalkyl,
2 0.78 40
2
-Oalkyl, -NC>2, -NH2, -NHalkyl or -NfalkylJjr each alkyl moiety having 1 to 4 carbon atoms.
Preferred compounds according to the invention are those of the formula wherein the various symbols are as defined above, and more 15 particularly those in which n is 2 or 3, X^ is a halogen atom or methyl, X2 is a halogen atom or methyl, R is -NI^, -OH or -ONa and Z is -CH2OCH3, -N(CH3)2 or -NH2.
According to the invention, the compounds of formula (I) can be prepared by reacting a benzophenone of the formula
Z
(II)
c=o
(II)
X
2
3
078 40
with a compound of the formula H2N-(CH2)n~COR if appropriate in the form of a salt, such as the hydrochloride. The reaction can be carried out at a temperature of 20 to 80°C and in a solvent, such as methanol.
The starting benzophenones (II) can be prepared by methods described in the literature.
Thus benzophenones of formula (II) in which Z is -COOalkyl, -COOH, -CONH2, -CONHalkyl or -CON(alkyl)2 can be prepared by reacting a compound of formula (III)
COOalkyl ch3
(III)
with a compound of formula (IV)
X
■ coc1
tr
(iv)
X3
in the presece of AlCl^ and in the solvent CH3N02 to provide a compound of formula (V)
COOalkyl
C = 0 (V)
2078 40
and, if desired, converting the -COOalkyl group into -COOH (as by treatment with NaOH), -CONH2 (as by treatment with ammonium hydroxide in acetone) or into -CONHalkyl or -CON(alkyl)2 (as by treatment with, say, CH^Nt^ in methanol).
Those benzophenones of formula (II) in which Z is -CH2OH or -CH20alkyl can be prepared by reacting a compound of formula (VI)
(VI)
with bromine in dichloromethane solvent in the presence of benzoyl peroxide, under reflux conditions, to provide a compound of formula (VII)
(VII)
and converting the -CH2Br group of the compound of formula (VII) into the group Z by treatment with water (Z = -CH2OH)
2 07840
or an alcohol such as methanol (Z = -COOalkyl) , under reflux conditions.
Benzophenones of formula (II) in which Z is -Oalkyl may be prepared by reacting a compound of formula (IV) above with a compound of formula (VIII)
Oalkyl
(VIII)
in chloroform in the presence of triethylamine to provide a compound of formula (IX)
Oalkyl
C0C1
(IX)
the compound of formula (IX) is introduced into a photochemical reactor with a benzene compound of formula (X)
X,
(X)
and the mixture is irradiated for 20 hours in a nitrogen atmosphere.
2 07840
Finally, benzophenones of formula (II) in which Z is -N02, -NH2, -NHalkyl or -N(alkyl)2 can be prepared by reacting a compound of formula (XI)
X
(XI)
X,
in acetic acid with KNO^ dissolved in H2SO^ and, if desired, converting the resulting benzophenone of formula (II) in 15 which Z is -N02 into a benzophenone of formula (II) in which Z is -NH2, -NHalkyl or -N(alkyl)2 in known manner (as by reducing the ~N02 group to -NH2 with hydrogen in the presence of Raney nickel, using a solvent such as ethanol).
The following Examples illustrate the invention. 20 The structure of the compounds are confirmed by analyses and IR and NMR spectra.
2 078 40
Example 1
4-£[(4-Chlorophenyl)-(5-ch lo ro-2-hydroxy-3-metho xyphenyI)-methyleneDamino^j-butanamide.
.4 cm' of an ethanolic 0.27 N solution of 5 sodium ethylate (that is to say 2.8 mmol) and 0.8 g
(2.69 mmol) of 45-dich loro-2-hydroxy-3-methoxybenzophenone are added to a suspension of 0.37 g (2.69 mmol) of^-aminobutyramide hydrochloride in 20 cm' of absolute ethanol.
The mixture is heated to the reflux temperature for 1 hour and 20 cm' of alcohol are distilled off. 200 cm' of absolute alcohol are added and the same volume is distilled off again.
After evaporation to dryness, 20 cm' of water are 15 added to the residue and the mixture is extracted with methylene chloride.
The extract is washed with water and aried over MgSO^ to give, on evaporation, a residue, which is re-crystallised from absolute ethanol. After washing with 20 petroleum ether and drying at 100°C in vacuo for 8 hours, the product, of melting point 209-10°C, is obtained.
2 07840
Examp le 2
4-|c(4-Chlorophenyl)-(5-chloro-2-hydroxy-3-n)ethoxymethyl-pheny I)-methyleneDami noj-butanoic acid and its sodium salt.
1. 5 g (1.61 x 10-2 mol) of (4-c h lo roph eny I) - (5-c h lo ro-2-hydroxy-3-methoxymethyIphenyI )-methanone, 300 ml of methanol, 3.1 g (3 x 10"^ mol) of Y'aminobutyric acid and 1.6 g (3 x 10~2 mol) of sodium methylate are introduced into a 1 litre flask.
The reaction mixture is brought to the reflux tem perature for 8 hours and is evaporated to dryness, the residue is taken up in 1.8 litres of distilled water and the mixture is acidified to pH 4.5 by addition of citric acid. The mixture is extracted with two 400 ml portions of 15 methylene chloride, the organic phases are combined,
washed with 500 ml of water, dried over NajSO^ and filtered and the filtrate is evaporated to dryness.
The acid obtained is recrysta 11 ised from 25 ml of methanol.
Melting point = 104 - 105°C.
2. 4.7 g (1.19 x 10 mol) of the acid obtained above, 100 ml of methanol and 9.7 ml of sodium methylate solution (1.22 N) are introduced into a 500 ml flask. The reaction mixture is evaporated at 60°C, 200 ml of pen-25 tane are introduced and the mixture is stirred for 10 minutes.
After filtration, draining and drying 'in a desic-
2 07840
cator at 60°C in the presence of t^,e' sodium salt is obtained.
Melting point = 136°C.
Example 3
U-\C(4-Ch lorophenyl)- (5-ch loro-2-hydroxy-3-dimethylamino-phenyl)-methylene3amino^-butanamide.
2.35 g (0.017 mol) of ^-aminobutyramide hydrochloride, 500 ml of ethanol, 17 ml of a molar solution of sodium methylate and 5.3 g (0.017 mol) of (4-chloro-10 phenyl)-(5-chloro-2-hydroxy-3-dimethylaminophenyl)-methanone are introduced into a flask.
The reaction mixture is heated to the reflux temperature and the ethanol is distilled off.
The mixture is evaporated to dryness, the residue 15 is taken up in water and chloroform and the organic phase is decanted, dried over magnesium sulphate and evaporated.
The residue is triturated in pentane, filtered off and recrysta 11 ised from a mixture of ethyl acetate/iso-propylether.
Melting point = 144.5 - 145°C.
207840
The structure and properties of compounds of formula (I) are summarised in Table I.
TABLE I
Compounds n
X1
X2
X3
Z
R
Melting point (°C)
1
3
-Cl
4-C1
h
C00CH3
NH2
168-169
2
3
-Cl
4-C1
H
COOCH3
OH
141-142
3
3
-Cl
4-Cl h
CONH2
nh2
143-144
4
3
-Cl
4-C1
H
COOH
OH
235-236
=
3
S-Cl
4-C1
rj orv
...2
- -1 ->
107- =
6
0
-Cl
4-Cl
U
CH^OH
NH2
153 . 5-9 . 5
7
3
-Cl
4-Cl
H
CM -,CCH ,
OH
T /-s A C
lijn - b
8
' 3
-Cl
4-Cl u
CH,0CH,
O'la
13 6 (decompo
sition)
Q
y
3
-Cl
4-Cl
H
CONH,
OH
214-5
3
-Cl
4-Cl
H
C0NHC,H-
MH7
202-3
11
3
-Cl
4-Cl
H
C0N'HCH3
nh2
24 2-3
12
3
-Cl
4-Cl
H
OCH
OH
153-4
13
3
-Cl
4-Cl
H
coi:hc3k7
ON a
160-1
14
3
-Cl
4-Cl u
C0NHCH3
ON a
> 250 (de-
composition)
2 0/8 40
TABLE x (continued)
Compounds n
X1
X2
X3
fl z
R
Melting point (°C)
3
-Cl
4-Cl h
OCH3
nh2
209-210
16
3
-Cl
4-Cl
II
NO 2
NH2
166-7
17
3
-Cl
4-Cl h
M(CH3)2
ON a
153-158
18
3
-Cl
4-Cl h
N(CH 3)2
nh2
144 . 5-5
19
3
-Cl
4-Cl
H
no2
ON a
163-165
3
-Cl
4-Cl
H
NE,
ON a
257-9
21
3
-Cl
4-Cl
H
NH0
NH0
219-220
22
3
-Cl
4-Cl
H
CONHC3H?
OH
216-7
23
-J
-Cl
4-Cl
H
1 1
COMHCHjj OH
218-9
24
3
-Cl
4-Cl
H
N(CH 3)2
, OH
159-160
-Cl
4-Cl
I
H
NO 2
{
| OH
206-208
i
2 6
3
-Cl
4-Ci!
1
U
NH,
i-
'OH
16 9 - 17 C
The structure and properties of starting benzophenones of formula (II) are summarised in Table II.
TABLE II
Compounds x1
X2
X3
z
Melting point (°C)
1
-Cl
4-Cl h
c02ch3
114-115
2
-Cl
4-Cl h
conh2
205-206
3
-Cl
4-Cl h
co2h
198-199
4
-Cl
4-Cl h
ch2och3
95-97
-Cl
4-Cl h
ch20h
102-103
6
-Cl i—1
u i
h conhc3h7
103-104
-J
/
-Cl
4-Cl u
C0NHCH3
169-170
8
-Cl
4-Cl k
och,
142 . 5-142
9
--1
4-Cl
* •*
no 2
112-112 . 5
-Cl
4-Cl
H
.+■ 0
N (pw n r i. 3 ' 2
u
164-166
11
-Cl
4-Cl h
nh ?
9 4 . 5-9 5
2078 40
Hydroxylated diphenylazomethines according to the invention have been subjected to tests on mice demonstrating their action on the central nervous system.
The antidepressive activity of the compounds was 5 demonstrated by antagonism to head twitches caused by L-5-hydroxytriptophan (L-5-HTP) in mice.
The mice (CDI males, Charles River France; 18-22 g body weight) received increasing doses of the products to be studied, or the solvent, subcutaneously, together with 10 L-5-HTP in a dose of 250 mg/kg. 45 minutes after this injection of L-5-HTP, the number of head twitches of each mouse is counted for one minute.
For each treatment, the average number of head twitches and the percentage variation relative to a control group are 15 calculated.
AD^q (50% dose or dose which reduces the average number of head twitches by 50%) is determined from the dose-effect curve by the graphical method of Miller and Tainter (1944).
AD,-g on interperitoneal administration of the compounds 20 according to the invention varies from 40 to 60 mg/kg.
The anticonvulsive activity of the compounds was demonstrated by antagonism to the mortality induced by bicuculline in mice.
Bicuculline is a relatively selective blocker of 25 post-synaptic GABA-ergic receptors and its convulsive and lethal effects are antagonised by compounds which increase
2 078 40
the level of cerebral GABA or have a GABA-mimetic activity.
The 50% active dose (AD^q), that is to say the dose which protects 50% of the animals from the effect of bicuculline, of the substances studied was evaluated. 5 AD50 on intraPeritoneal administration of the compounds according to the invention varies from 10 to 100 mg/kg.
The compounds according to the invention are active antidepressants and anticonvulsants and also have antiulcer, anxiolytic,analgesic and antiinflammatory properties. They 10 can be used in human and veterinary therapy for the treatment of various diseases of the central nervous system, for example for the treatment of depressions, psychoses and some neurological diseases, such as epilepsy, spasticity and dyskinesia.
The invention accordingly relates to all pharmaceutical compositions containing the compounds (I) as active principles together with any excipients suitable for their administration, in particular oral (tablets, coated tablets, gelatine capsules, capsules, cachets and solutions or 20 suspensions for oral use) or parenteral administration.
The daily posology may be from 100 to 3,000 mg.
2 ©78 40
Claims (7)
1. A hydroxylated diphenylazomethine of the formula (I) Z 10 in which n is an integer from 1 to 4, X^, X2 and X^, which may be the same or different, each represent a hydrogen atom, a halogen atom, -OCH^ or a straight-chain or branched C. .-alkyl group, R represents -NH_, -OH or -OM P (wherein M represents an alkali metal or alkaline earth 15 metal of valency p) and Z represents -COOH, -COOalkyl, -CONH2, -CONHalkyl, -CON(alkyl)2, -CH2OH, -CH2Oalkyl, -Oalkyl, -N02, -NH2, -NHalkyl or -N(alkyl)2, each alkyl moiety having 1 to 4 carbon atoms.
2. A compound according to claim 1, of the formula 20 2Q78 4< - 16 - C=N-(CH-) -COR i - n wherein the various symbols are as defined in claim 1.
3. A compound according to claim 1 or 2, in which n is 2 or 10 3, X^ is a halogen atom or methyl, X2 is a halogen atom or methyl, R is -NH2, -OH or -ONa and Z is -CH20CH3, -N(CH3)2 or -nh2.
4. A hydroxylated diphenylazomethine according to claim 1 substantially as described with reference to any one of 15 Compounds 1 to 28 in Table I.
5. A process for the preparation of a hydroxylated diphenylazomethine as claimed in claim 1, which comprises reacting a benzophenone of the formula (II) z X1 25 (ii) with a compound of the formula H2N-(CH2)n~COR, the various symbols being as defined in claim 1. 2078 40 - 17 -
6. A process according to claim 5 substantially as described with reference to Example 1, 2 or 3.
7. A pharmaceutical composition which comprises as active ingredient at least one hydroxylated diphenylazomethine as * r ■» claimed in any one of claims 1 to 4, together with a pharmaceutical^ acceptable excipient. ^ — ;jir Authorised Agents, A. J. PARK & SON N.Z. PATENT OFFI'. £ 13 APR 1914
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8306082A FR2544309B1 (en) | 1983-04-14 | 1983-04-14 | HYDROXYLATED DIPHENYLAZOMETHINES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ207840A true NZ207840A (en) | 1986-02-21 |
Family
ID=9287836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ207840A NZ207840A (en) | 1983-04-14 | 1984-04-13 | Diphenylazomethine derivatives and pharmaceutical compositions |
Country Status (20)
| Country | Link |
|---|---|
| JP (1) | JPS59199665A (en) |
| AU (1) | AU2682584A (en) |
| BE (1) | BE899423A (en) |
| DE (1) | DE3414051A1 (en) |
| DK (1) | DK191684A (en) |
| ES (1) | ES531605A0 (en) |
| FI (1) | FI841484A (en) |
| FR (1) | FR2544309B1 (en) |
| GB (1) | GB2138000A (en) |
| GR (1) | GR79857B (en) |
| HU (1) | HUT34153A (en) |
| IL (1) | IL71540A0 (en) |
| IT (1) | IT1176042B (en) |
| LU (1) | LU85311A1 (en) |
| NL (1) | NL8401189A (en) |
| NO (1) | NO841486L (en) |
| NZ (1) | NZ207840A (en) |
| PT (1) | PT78429B (en) |
| SE (1) | SE8402082L (en) |
| ZA (1) | ZA842798B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1212000B (en) * | 1987-12-24 | 1989-11-08 | Sigma Tau Ind Farmaceuti | PHENYLBENZYLIDEN-DERIVATIVES OF ACID 3) AMINOPROPANSULPHONIC WITH ANTI-CONVULSIVE ACTIVITY AND THEIR PHARMACEUTICAL COMPOSITIONS FOR THE THERAPEUTIC TREATMENT OF EPILEPSY |
| FR2788768B1 (en) | 1999-01-21 | 2001-02-16 | Oreal | NEW CATIONIC 2-ACYLAMINOPHENOLS, THEIR USE AS COUPLER FOR OXIDATION DYEING, COMPOSITIONS COMPRISING THEM, AND DYEING METHODS |
| FR2788691B1 (en) | 1999-01-21 | 2002-06-14 | Oreal | COMPOSITIONS FOR OXIDATION DYEING OF KERATINIC FIBERS COMPRISING A CATIONIC COUPLER, NOVEL CATIONIC COUPLERS, THEIR USE FOR OXIDATION DYEING, AND DYEING METHODS |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2319338A1 (en) * | 1975-08-01 | 1977-02-25 | Synthelabo | NEW A-PHENYL BENZYLIDENIC DERIVATIVES OF AMINO ACIDS, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM |
| FR2516509B1 (en) * | 1981-11-18 | 1985-07-26 | Synthelabo | BENZYLIDENIC DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
| FR2430936A1 (en) * | 1978-07-13 | 1980-02-08 | Synthelabo | Alpha-phenyl 2-hydroxy-benzylidene amino-alkanoic acid derivs. - and novel di:phenyl-ketone intermediates, useful as anticonvulsants for treating epilepsy |
-
1983
- 1983-04-14 FR FR8306082A patent/FR2544309B1/en not_active Expired
-
1984
- 1984-04-13 BE BE0/212765A patent/BE899423A/en not_active IP Right Cessation
- 1984-04-13 ES ES531605A patent/ES531605A0/en active Granted
- 1984-04-13 PT PT78429A patent/PT78429B/en unknown
- 1984-04-13 DK DK191684A patent/DK191684A/en not_active Application Discontinuation
- 1984-04-13 ZA ZA842798A patent/ZA842798B/en unknown
- 1984-04-13 NO NO841486A patent/NO841486L/en unknown
- 1984-04-13 FI FI841484A patent/FI841484A/en not_active Application Discontinuation
- 1984-04-13 IT IT20528/84A patent/IT1176042B/en active
- 1984-04-13 AU AU26825/84A patent/AU2682584A/en not_active Abandoned
- 1984-04-13 HU HU841456A patent/HUT34153A/en unknown
- 1984-04-13 JP JP59075679A patent/JPS59199665A/en active Pending
- 1984-04-13 SE SE8402082A patent/SE8402082L/en not_active Application Discontinuation
- 1984-04-13 GB GB08409686A patent/GB2138000A/en not_active Withdrawn
- 1984-04-13 LU LU85311A patent/LU85311A1/en unknown
- 1984-04-13 GR GR74421A patent/GR79857B/el unknown
- 1984-04-13 DE DE19843414051 patent/DE3414051A1/en not_active Withdrawn
- 1984-04-13 NZ NZ207840A patent/NZ207840A/en unknown
- 1984-04-13 IL IL71540A patent/IL71540A0/en unknown
- 1984-04-13 NL NL8401189A patent/NL8401189A/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IT1176042B (en) | 1987-08-12 |
| HUT34153A (en) | 1985-02-28 |
| FI841484A0 (en) | 1984-04-13 |
| ES8502677A1 (en) | 1985-01-16 |
| GB2138000A (en) | 1984-10-17 |
| PT78429A (en) | 1984-05-01 |
| LU85311A1 (en) | 1985-11-27 |
| JPS59199665A (en) | 1984-11-12 |
| FI841484A (en) | 1984-10-15 |
| FR2544309B1 (en) | 1986-01-10 |
| SE8402082L (en) | 1984-10-15 |
| ES531605A0 (en) | 1985-01-16 |
| NL8401189A (en) | 1984-11-01 |
| ZA842798B (en) | 1984-11-28 |
| SE8402082D0 (en) | 1984-04-13 |
| AU2682584A (en) | 1984-10-18 |
| DE3414051A1 (en) | 1984-10-18 |
| PT78429B (en) | 1986-08-22 |
| IL71540A0 (en) | 1984-07-31 |
| NO841486L (en) | 1984-10-15 |
| BE899423A (en) | 1984-10-15 |
| GR79857B (en) | 1984-10-31 |
| DK191684A (en) | 1984-10-15 |
| IT8420528A0 (en) | 1984-04-13 |
| DK191684D0 (en) | 1984-04-13 |
| FR2544309A1 (en) | 1984-10-19 |
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